OBJECTIVES: A. Overall: 1. General: To attempt to quantify the interrelationships, distinguish between causes and consequences, evaluate the relative role of environmental and genetic factors and understand the temporal sequence of events in the complex of glucose intolerance - obesity - macro and micro vascular complications. 2. Specific: A nationwide sample of 5600 Jewish residents, born 1912-1941, stratified by sex, age, place of birth and length of residence in Israel is being followed prospectively in three phases. In phase I (1968-72) ten consecutive once-daily blood pressure measurements, weight, height and morbidity information were collected on each individual at home. In phase II, (which started at the end of 1976), about 1500 phase I participants were examined for oral glucose tolerance (OGT), urea, ECG, weight, morbidity and mortality. Phase III, (1979- ) funded by the current grant, comprises four parts: Main study: consists of examinations of 4000 phase I participants by the main set of examinations namely: the above listed phase II examinations as well as determination of glycolsylated hemoglobin (HbA1) insulin response curve (IRC), high, low and very low density lipoproteins (HDL, LDL, and VLDL) and creatinine. Dietary study: About 1200 detailed dietary interviews in all overt diabetics and a sample of persons with chemical diabetes and with normal glucose tolerance. High molecular weight proteinuria study: In the dietary study group presence of high molecular weight proteinuria will be determined. Drug study: In an estimated 600 persons on oral hypoglycemic and/or antihypertensive drugs, urine, and serum drug concentrations will be determined for assessment of compliance, factors affecting response to these drugs and the interrelation of drug therapy with morbidity.